THE CREATION of The Ellison Medical Foundation grew out of a series of conversations in the early 1990s between two men. One was Lawrence J. Ellison, the founder and Chief Executive Officer of Oracle, the giant software corporation specializing in information management. The other was Dr. Joshua Lederberg, the Nobel Prize winning biologist known for his innovative thinking about the intersections of science and society

The two men met after Mr. Ellison heard Dr. Lederberg speak at Stanford University on the applications of artificial intelligence to biology. "I got a note from Larry saying he was very interested and would like to hear more next time I'm out in California," recalled Dr. Lederberg, who is President Emeritus of The Rockefeller University in New York. "It took a year, but I contacted him. He invited me to his house, I oohed and aahed, and he said, 'It's obvious you like the house — so stay here.' At one point he gave me a key to the house and said, 'I never want to hear about you staying anywhere else.' "

After their first meeting, Dr. Lederberg said, he visited Mr. Ellison whenever he had business in the area, every two or three months, staying four or five days each time. Over dinner in what Dr. Lederberg called "the most gorgeous setting in the world," they talked of many things, including the way great wealth could be used. "Eventually I think he came to trust me and that I would look out for his interests," Dr. Lederberg said. "I didn't have any interest of my own, except that I was eager that he not die rich — that would be foolish."

Mr. Ellison said that he would have liked to do molecular biology as an alternative career, so Dr. Lederberg invited the software entrepreneur to work in his lab at Rockefeller in 1994. "He spent two weeks here being de facto my daughter's lab assistant in work we were doing on mutagenesis and E. coli," Dr. Lederberg said. "He snapped that up very quickly and within a day or two he was participating in discussions about what to do."

In fact, Dr. Lederberg said, "He asked one question that profoundly altered what we did — it punctured holes in our control mechanism. It made it clear that we'd have to redo the experiment." Later on, they talked about different fields for the foundation "and aging was one that stuck," Dr. Lederberg said. "It was clear it was an area that was not quite integrated into what most molecular biologists were doing."

So the non-profit Foundation was created, with Dr. Lederberg as head of a Scientific Advisory Board of six distinguished scientists that approves the Foundation's grants.

Their approach was clear before the first staff person was hired: The Foundation would fund people, not projects. It would look for smart people who had track records of creative, productive work and who had a good idea. Then it would give them money and stand back. It would favor basic research that was too risky or speculative to attract mainstream funding. Applications would be simple, a short letter rather than a book-length treatise. Researchers would have the flexibility to pursue their research wherever it led.

"Josh and I had lunch, and Josh described Larry Ellison's plans for a new foundation," Dr. Richard L. Sprott recalled. "Then I called my wife and said, 'I just took a job, and I have no idea where we'll live or what it pays, but it's too good to pass up.'"

Dr. Sprott became the new Foundation's Executive Director in 1998, after years directing the National Institute of Aging's Biology of Aging Program. "It was like dying and going to heaven," he said. The Foundation made its first awards, for research into the basic biology of aging, in 1998. Dr. Sprott recalls one of the board's first meetings, attended by Larry Ellison. "We were choosing 10 scholars. We had chosen six, and had six or eight candidates for the remaining four grants. We were having difficulty deciding between them based on scientific merit. Finally Larry said, 'Fund them all. If they're so close you can't decide, fund them all.' And that sort of set the tone." Since those early days, Mr. Ellison has not been directly engaged in the Foundation's operations, although he provides all its funds. "He has expressed several times that I'm going to leave it to you to run," Dr. Lederberg said. "'You've got the smartest people in the world working on it."

The Foundation got underway just as a series of discoveries about genetic influences on lifespan in various experimental organisms "set the grass on fire," in the words of Dr. Gordon J. Lithgow, a 2002 Senior Scholar.

"The Ellison was a great thing," Dr. Lithgow said. "It was like the stamp of approval. Here was a foundation saying this was really important. This was a big boost for people. I know the major people in the field were really excited. "Ellison's approach — small applications, looking for really hot ideas — that was timely because a lot of people had really, really good ideas, and it would take the NIA time to catch up."

Or, as Dr. Sprott put it: "We have this very radical idea that people who do the research are better able to know what they should do than administrators are."

In addition to the Foundation's Aging Program, in 2000 Mr. Ellison decided to establish a program on Global Infectious Disease. The first GID scholar awards were made in 2001. The following year, the Foundation added a deputy director, Stephanie L. James, to run the GID Program. Prior to joining Ellison, Dr. James had been Chief of the Parasitology and International Programs Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH.

"The GID program really was aimed at a specific niche that was not well covered by the disease funders," Dr. James said. "The niche was the aspects that fall between the mandates of different organizations — things like microbial ecology or zoonotic infections." The program also supported collaborations between disciplines that haven't collaborated in the past. "The aim of the program was to fill a gap and the gap is an important one," she said. Dr. James left the Foundation in 2004 to join the Foundation for the National Institutes of Health as Associate Director for science for the Grand Challenges in Global Health initiative.

In 2005, Mr. Ellison decided to discontinue the GID program, which stopped accepting new applications. As of this writing, he was exploring other ways to expand his philanthropy in the area of global health.

In 2001, the volume of grants led the Foundation to establish Initial Review Groups, panels of five or six scientists in each program who examine grant applications and make recommendations to the Scientific Advisory Board.

"When we first did it, we worried that the Foundation's point might get blunted," Dr. Sprott said. But the reviewers, who are distinguished scientists themselves, including several Ellison Scholars, have been careful to retain the focus on innovation.

"We are very aware of the goals of the foundation," said Dr. Phyllis Wise, a 2001 Senior Scholar who now serves on the review panel. "If we get an application we think could be funded by NIH, we don't fund it, we tell them to apply there." In 2005, the Foundation received letters of application from 297 potential Senior Scholars, 50 more than the previous year, and almost 60 nominations for New Scholar Awards. In its first year, the Foundation received even more Senior Scholar letters — 302 — but many were not on target because the Foundation's priorities were not well-known. Now, a high proportion of applicants are on target, making choosing among them more difficult and time-consuming.

Not surprisingly, funded scientists appreciate The Ellison Medical Foundation's willingness to take a chance. As Dr. Lederberg noted dryly, "Not many creative scientists would dissent from what we're trying to do."

"The help I got from The Ellison Medical Foundation was extra timely because we were at the stage when we were trying new technologies," said Dr. Fernando Nottebohm, a 2001 Senior Scholar. "We needed someone who would give us the elbow room to make mistakes."

"I'm very, very supportive of Ellison. I think they've made a big difference in science," said Dr. Sherilynne Fuller, who received a 2000 Infrastructure Award for her Telemakus information system. "They take a chance on the person."

Photo following The Ellison Medical Foundation Symposium on "The Biology of Aging and Global Infectious Diseases" held September 19, 2002 at Stanford University School of Medicine